Odors play an increasingly appreciated role in our general quality of life and well being, a role that is compromised by the effect of disease, drugs, aging and environmental onslaught on olfactory competence. Primary olfactory receptor neurons serve the critical function of detecting and transducing odor stimuli. Disruption of any of the cellular processes leading to receptor cell activation would impair olfactory function. Particularly important targets would be gain-setting processes that are known to be critical control points in biological systems. Olfactory transduction is a two-stage process in which odors activate a primary second messenger cascade that secondarily triggers the main excitatory current for the cell. This strategy for achieving high-gain, low-noise amplification appears to be a fundamental organizational principle that has been conserved or converged upon in evolution. This continuing project combines electrophysiological and molecular approaches to (l) identify the factors that regulate the mail output channel and (2) further define the steps that lead to activation of this channel. The project uses an invertebrate animal model in which both phosphatidylinositol and cyclic nucleotide signaling lead to activation of the output channel. It builds on interesting preliminary evidence that what were considered to be inactive products of phosphatidylinositol metabolism, an intracellular signaling system that has been implicated in olfactory transduction in a conflicting and even controversial way, can regulate the output channel.